Various clinical examinations carried out for the diagnosis, treatment or prevention of diseases are essential in contemporary medical science. Particularly, clinical biochemical examinations, for analyzing particular compounds, occupy an important position in the clinical medical science. Furthermore, following development of the basic medical sciences and advancement of analyzing techniques, attempts have been made to enlarge the extent of samples to be examined and items to be measured. Attempts have also been made at improving measurement accuracy and automating measuring techniques at various measuring stages. Such attempts include developing abbreviated rapid measurement systems for urgent or bedside measurement, or systematized measurements carried out in large-scale hospitals.
Samples used in clinical biochemical examinations at the present time are generally blood and urine.
Blood provides quite ample information and allows several hundred items to be measured. However, collecting blood causes subjects or patients physical pain and the loss of their important blood. Repeated collection of blood and a continuous measurement thereof imposes a heavy burden on the subjects or patients. In addition, analyzing the blood samples is dealt exclusively or centrally by a blood analysis center (firms specialized in blood analysis), occupying significant time from blood collection to analysis. This time delay leads to larger errors in measurement of certain blood contents, which are easily gasified or denatured. Hence, such unstable components are accurately measured only at large-scale hospitals equipped with special analyzing apparatuses.
Urine is broadly used in screening. It is relatively easily and amply collectable, but provides less information than blood does, which is a problem. Also, the method of collecting urine samples can be embarrassing to the patient, and does not facilitate continuous measurement. Urine samples are also hard to collect at times.
Other bloodless and noninvasive clinical analyzing techniques aside from the urine analyzing techniques have been developed. For example, some analyzing techniques sample other body fluids such as exudate from skin (lymph), sweat, saliva or the like, or percutaneously measure blood gas with a blood gas sensor. But, these techniques have not been broadly used, since less samples are obtainable, and measurable items are limited. Hence, the main stream of development of the clinical biochemical examination techniques is now directed to those which do not cause the subjects pain when collecting the blood sample, and which can measure a larger variety of items, typically available only in trace quantities in the blood samples.
In any case, conventional clinical biochemical examinations require considerable labor and specialized techniques for collecting, transporting, preserving, separating and analyzing samples such as blood and urine. These techniques create problems with examination accuracy. They are slow and labor intensive, and cause the subjects (patients) unnecessary pain. Solving these problems will not only be beneficial to the patients, but also to the health care professionals engaged in medical treatment.
It is said that doctors having considerable experience in medical treatment can judge the identity of diseases from distinct odors emitted by the patients, and can use the odors in treating their patients. For example, expiratory air exhaled by a patient with diabetes can smell like acetone or can have a particular sweet smell. The odor of exhaled gas from a patient with a liver sickness or leukemia might resemble that of ammonia or sulfide. However, this information is obtainable from a doctors experience: it may be judged differently by specific doctors and cannot be objectively shown by data. Also, the clinical biochemical examinations using subjects' exhaled air as samples have been put to little practical use, and basic studies thereof have not been advanced, the reasons for which are twofold.
First, there is a prejudice in the art that expiratory air is not usable as a sample for clinical biochemical examination. Second, because gases to be detected in expiratory air are quite low in concentration (ppb or ppm at the most), they are measurable only by combining a concentrating device to concentrate the trace gas component with a large-scaled high-sensitivity gas detecting device. Hence, measurement of the samples can be carried out only in a laboratory provided with special instruments and equipment, which necessitate the presence of skilled operators to operate them.
There have been only a few clinical reports that discuss expiratory gas measurement. Such clinical reports include: (1) Dubowski, K,M, Breath Analysis as a Technique in Clinical Chemistry, Clin Chem., 20.966-972, 1974, (2) Manolis,A., The Diagnostic Potential of Breath Analysis, Clin. Chem., 29. 5-15, 1983, and (3) Phillips, M., Breath Tests in Medicine, Scientific American July 1992. These reports disclose measurement and observation data only.
Expiratory air, or exhaled air, is intermittently breathed out by human (or animals) during their lives. It is readily collectable, without causing the subject physical or mental pain. This noninvasive collection technique is particularly well suited for infants and patients with serious illness or damaged consciousness. Also, since trace amounts of a volatile component of mixed venous blood flowing through the alveolar blood capillary is moved into expiratory air by gas exchange, it is inferred that expiratory air and blood are correlated with respect to the volatile component. Furthermore, examinations of expiratory air enables differential measurement of the volatile components which blood analysis could not disclose. Thus, expiratory air is an ideal sample for the clinical biochemical examination.
Expiratory air, when collected in vessels, requires considerable space for preservation and transportation and some gas components subject to examination are unstable, so that they are not well suited to the analysis path normally taken by blood samples: i.e., being first transported to the analysis center and then analyzed by the large-scale apparatuses. That is, it is highly desirable that the clinical biochemical examination using expiratory air as a sample is carried out "on-site". Expiratory air may be effectively used when the gas measurement occurs while the patient is being attended to by the measuring operator, or while the patient is connected to the measuring device. For example, bedside examination, prehospital examination in an ambulance, screening upon medical examination and monitoring of patient status (continuous monitoring) are all suitable applications.
The previously mentioned apparatus, comprising the combination of the concentrating device and the large-scale high sensitivity gas detecting device, used in some local laboratories, is not practically appropriate for the clinical biochemical examination using expiratory air as samples. A practical clinical use of expiratory gas analysis requires an examination device which is small-sized, portable, of high sensitivity, simply operable and superior in safety and rapidity in measurement. Reliability of provided data and economization in use of such examination device are also required. Furthermore, since it is possible that moisture of expiratory air in a container makes dew on a wall of the container to dissolve and adsorb trace amounts of gas components, for such a device it is preferable that expiratory air from a subject (patient) is sucked directly into the device to be subjected to measurement.